Drug Development for NAFLD: Landscape and Challenges

Publication date: Available online 13 March 2019Source: Journal of Clinical and Experimental HepatologyAuthor(s): Prarthana Thiagarajan, Guruprasad Padur AithalAbstractNon-alcoholic fatty liver disease (NAFLD) is now the leading cause of chronic liver disease in industrialised economies. With no licensed treatment currently available, together with a growing prevalence that parallels global increases in obesity and type 2 diabetes, NAFLD will dominate the landscape of hepatology for the foreseeable future. A multifaceted aetiopathogenesis, paucity of reproducible pre-clinical models that effectively recreate human NAFLD and lack of robust surrogate trial endpoints have presented major hurdles in drug discovery and development. Smooth collaboration between bench scientists, biotechnology, pharmaceutical industries and clinicians will be pivotal to target identification, development of effective therapies, biomarker discovery and ultimately to bring pipeline drugs to market. This review examines the key challenges remaining in NAFLD drug development, outlines early and late phase clinical trials of candidate treatments and discusses the journey towards biomarker discovery which may facilitate development of novel endpoints in NAFLD clinical trials, enabling meaningful response to be determined non-invasively.
Source: Journal of Clinical and Experimental Hepatology - Category: Gastroenterology Source Type: research

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AbstractThe World Health Organization defines overweight and obesity as the condition where excess or abnormal fat accumulation increases risks to health. The prevalence of obesity is increasing worldwide and is around 20% in ICU patients. Adipose tissue is highly metabolically active, and especially visceral adipose tissue has a deleterious adipocyte secretory profile resulting in insulin resistance and a chronic low-grade inflammatory and procoagulant state. Obesity is strongly linked with chronic diseases such as type 2 diabetes, hypertension, cardiovascular diseases, dyslipidemia, non-alcoholic fatty liver disease, chr...
Source: Intensive Care Medicine - Category: Intensive Care Source Type: research
Metabolic disorders such as insulin resistance, obesity, and hyperglycemia are prominent risk factors for the development of non-alcoholic fatty liver disease (NAFLD)/steatohepatitis (NASH). Dietary rodent mod...
Source: BMC Gastroenterology - Category: Gastroenterology Authors: Tags: Research article Source Type: research
AbstractAimTo investigate whether GE is affected in children/adolescents with obesity and abnormalities of the metabolic syndrome (MetS).MethodsCross-sectional study of oral GE (oGE), insulin sensitivity and secretion (calculated on 5 time-points oral glucose tolerance test) and metabolic abnormalities in 1012 patients with overweight/obesity (aged 6.0 –17.9 years old). A MetS risk score was calculated on the basis of distribution of fasting glucose, triglycerides, HDL-cholesterol, total cholesterol, systolic and diastolic blood pressure. Non-alcoholic fatty liver disease (NAFLD) was suspected based on thresholds of ...
Source: Acta Diabetologica - Category: Endocrinology Source Type: research
Authors: Laursen TL, Hagemann CA, Wei C, Kazankov K, Thomsen KL, Knop FK, Grønbæk H Abstract Non-alcoholic fatty liver disease (NAFLD) is increasingly recognized as a significant liver disease, and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis (NASH) to fibrosis, subsequent cirrhosis, end-stage liver failure, and liver cancer with a potential need for liver transplantation. NAFLD and NASH are closely related to obesity, metabolic syndrome, and type 2 diabetes (T2D). The role of gut hormones, especially glucagon-like peptide 1 (GLP-1), i...
Source: World Journal of Hepatology - Category: Gastroenterology Tags: World J Hepatol Source Type: research
FINDINGSIn a comprehensive, nine-year-long study in mice, researchers profiled more than 300 liver and plasma lipid species and more than 5,000 liver proteins. The combined data helped researchers to identify new mechanisms that control the metabolism of lipids (molecules that include fat) and to discover a protein that regulates lipids. They found that silencing one particular protein, called PSMD9, is a potential therapeutic strategy to reduce nonalcoholic fatty liver disease.BACKGROUNDNonalcoholic fatty liver disease is the buildup of excess fat in liver cells not caused by alcohol. The disease affects about 25 percent ...
Source: UCLA Newsroom: Health Sciences - Category: Universities & Medical Training Source Type: news
ConclusionIn this review, I will summarize the current findings regarding the role of gut microbiome and metabolites in metabolic disorders to argue whether the current achievements may be translated into clinical practice.
Source: Journal of Endocrinological Investigation - Category: Endocrinology Source Type: research
AbstractPurpose of ReviewObesity has increased in South Asian countries that are still grappling with undernutrition. In this review, we highlight the characteristics of obesity, its relation to morbidities, and its management in South Asians. A literature search was conducted using relevant search engines and based on key words focusing on obesity in South Asians.Recent FindingsThe increasing trend in obesity prevalence is caused by imbalanced diets and physical inactivity. South Asians, in general, have higher body fat and lower skeletal muscle mass at the same or lower BMIs compared to white people ( “high body fa...
Source: Current Obesity Reports - Category: Eating Disorders & Weight Management Source Type: research
Abstract Recent studies have reported the positive association between exposure to insecticides and increased risk of obesity and type 2 diabetes, which are closely associated with non-alcoholic fatty liver disease (NAFLD). However, it is not known if insecticide exposure can contribute to NAFLD. Thus, the goal of the current study was to determine if insecticide exposures can exacerbate the physiological conditions of NAFLD by modulating hepatic lipid metabolism. The effects of 12 insecticides on triglycerides (TG) accumulation were tested using palmitic acid (PA)-induced HepG2 hepatoma steatosis model. Results s...
Source: Food and Chemical Toxicology - Category: Food Science Authors: Tags: Food Chem Toxicol Source Type: research
ConclusionThe occurrence of NAFLD in FDR of T2DM was influenced by IR (central obesity and obesity).
Source: Diabetes and Metabolic Syndrome: Clinical Research and Reviews - Category: Endocrinology Source Type: research
Publication date: Available online 29 January 2019Source: Pharmacology &TherapeuticsAuthor(s): William S. BlanerABSTRACTMuch evidence has accumulated in the literature over the last fifteen years that indicates vitamin A has a role in metabolic disease prevention and causation. This literature proposes that vitamin A can affect obesity development and the development of obesity-related diseases including insulin resistance, type 2 diabetes, hepatic steatosis and steatohepatitis, and cardiovascular disease. Retinoic acid, the transcriptionally active form of vitamin A, accounts for many of the reported associations. How...
Source: Pharmacology and Therapeutics - Category: Drugs & Pharmacology Source Type: research
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